3-12408029-G-T

Variant names:

• chr3-12408029-G-T
• rs796313
• NM_138711.6:c.729+1948G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138711.6(PPARG):​c.729+1948G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 151,964 control chromosomes in the GnomAD database, including 16,085 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.44 (16085 hom., cov: 31)
• Consequence: PPARG NM_138711.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.867
• Publications: 12 publications found

Genes affected

PPARG (HGNC:9236): (peroxisome proliferator activated receptor gamma) This gene encodes a member of the peroxisome proliferator-activated receptor (PPAR) subfamily of nuclear receptors. PPARs form heterodimers with retinoid X receptors (RXRs) and these heterodimers regulate transcription of various genes. Three subtypes of PPARs are known: PPAR-alpha, PPAR-delta, and PPAR-gamma. The protein encoded by this gene is PPAR-gamma and is a regulator of adipocyte differentiation. Additionally, PPAR-gamma has been implicated in the pathology of numerous diseases including obesity, diabetes, atherosclerosis and cancer. Alternatively spliced transcript variants that encode different isoforms have been described. [provided by RefSeq, Jul 2008]

PPARG Gene-Disease associations (from GenCC):

• PPARG-related familial partial lipodystrophy

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P, Genomics England PanelApp
• Berardinelli-Seip congenital lipodystrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138711.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARG	NM_138711.6	MANE Select	c.729+1948G>T		intron	N/A	NP_619725.3
	PPARG	NM_001354668.2		c.*1882G>T		3_prime_UTR	Exon 5 of 5	NP_001341597.1
	PPARG	NM_001354670.2		c.*1882G>T		3_prime_UTR	Exon 6 of 6	NP_001341599.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPARG	ENST00000651735.1	MANE Select	c.729+1948G>T		intron	N/A	ENSP00000498313.1
	PPARG	ENST00000287820.10	TSL:1	c.819+1948G>T		intron	N/A	ENSP00000287820.6
	PPARG	ENST00000397010.7	TSL:1	c.729+1948G>T		intron	N/A	ENSP00000380205.3

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67582 AN: 151846 Hom.: 16071 Cov.: 31

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.487

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.445 AC: 67620 AN: 151964 Hom.: 16085 Cov.: 31 AF XY: 0.445 AC XY: 33064 AN XY: 74252

African (AFR) AF: 0.274 AC: 11347 AN: 41408

American (AMR) AF: 0.503 AC: 7685 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 2136 AN: 3466

East Asian (EAS) AF: 0.424 AC: 2197 AN: 5180

South Asian (SAS) AF: 0.327 AC: 1574 AN: 4816

European-Finnish (FIN) AF: 0.537 AC: 5658 AN: 10544

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.517 AC: 35151 AN: 67966

Other (OTH) AF: 0.487 AC: 1030 AN: 2114

Alfa AF: 0.509 Hom.: 22826

Bravo AF: 0.442

Asia WGS AF: 0.400 AC: 1389 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.33
DANN	Benign	0.40
PhyloP100		-0.87
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs796313; hg19: chr3-12449528;